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      HBx promotes hepatocellular carcinoma progression by repressing the transcription level of miR-187-5p

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          Abstract

          HBV-associated hepatitis B virus x protein (HBx) plays multiple roles in the development of hepatocellular carcinoma. In our prior study, we discovered that miR-187-5p expression was inhibited by HBx. To investigate the underlying molecular mechanism of HBx-mediated miR-187-5p downregulation in hepatocellular carcinoma cells, effects of HBx and miR-187-5p on hepatoma carcinoma cell were observed, as well as their interactions. Through in vitro and in vivo experiments, we demonstrated that overexpression of miR-187-5p inhibited proliferation, migration, and invasion. Simultaneously, we observed a dysregulation in the expression of miR-187-5p in liver cancer cell lines, which may be attributed to transcriptional inhibition through the E2F1/FoxP3 axis. Additionally, we noted that HBx protein is capable of enhancing the expression of E2F1, a transcription factor that promotes the expression of FoxP3. In conclusion, our results suggest that the inhibitory effect of HBx on miR-187-5p is mediated through the E2F1/FoxP3 axis. As shown in this work, HBx promotes hepatoma carcinoma cell proliferation, migration, and invasion through the E2F1/FoxP3/miR-187 axis. It provides a theoretical basis for finding therapeutic targets that will help clinic treatment for HCC.

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          MicroRNAs: genomics, biogenesis, mechanism, and function.

          MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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            Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

            Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Funding Bill & Melinda Gates Foundation.
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              The broken cycle: E2F dysfunction in cancer

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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 August 2023
                01 August 2023
                : 15
                : 15
                : 7533-7550
                Affiliations
                [1 ]College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China
                [2 ]Hubei Institute of Blood Transfusion, Wuhan Blood Center, Wuhan 430033, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Jun Zhou; email: zhoujun@wust.edu.cn
                Correspondence to: Jingjiao Zhou; email: zhoujj@wust.edu.cn
                Article
                204921 204921
                10.18632/aging.204921
                10457053
                37531206
                14bc889b-9a9f-4236-b24a-3826c3284d0e
                Copyright: © 2023 Deng et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 February 2023
                : 23 June 2023
                Categories
                Research Paper

                Cell biology
                hepatocellular carcinoma,hbx,mir-187-5p,e2f1
                Cell biology
                hepatocellular carcinoma, hbx, mir-187-5p, e2f1

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